Unveiling the Genetic Landscape of Basal Ganglia: Implications for Common Brain Disorders
Bahrami, S.; Nordengen, K.; Rokicki, J.; Shadrin, A. A.; Rahman, Z.; Smeland, O. B.; Jaholkowski, P. P.; Parker, N.; Parekh, P.; OConnell, K. S.; Elvsashagen, T.; Toft, M.; Djurovic, S.; Dale, A. M.; Westlye, L. T.; Kaufmann, T.; Andreassen, O. A.
Show abstract
The basal ganglia are subcortical brain structures involved in motor control, cognition, and emotion regulation. We conducted a multivariate genome-wide association analysis (GWAS) to explore the genetic architecture of basal ganglia volumes using brain scans obtained from 34,794 European individuals with replication in 5,236 non-Europeans. We identified 72 genetic loci associated with basal ganglia volumes with a replication rate of 87.5%, revealing a distributed genetic architecture across basal ganglia structures. Of the 72 loci, 51 are novel. Of these, APOE, NBR1 and HLAA, are all exonic and among the novel loci. Furthermore, we examined the genetic overlap between basal ganglia volumes and several neurological and psychiatric disorders. The most prominent overlap was seen with Parkinsons disease, schizophrenia and migraine. HP and TMEM161B showed overlap between basal ganglia and Parkinsons disease, but also three different psyciatric or nevrodevelopmental disorder(s), demonstrating important shared biology between brain disorders. Functional analyses implicated neurogenesis, neuron differentiation and development in basal ganglia volumes. These results enhance our understanding of the genetic architecture and molecular associations of basal ganglia structure and their role in brain disorders.
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